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Viruses may cause or increase the risk of malignancy through several mechanisms, including direct transformation of cells and/or expression of oncoproteins. Epstein-Barr virus (EBV), a versatile lymphotropic g-type human herpesvirus or Lymphocryptovirus (LCV), is associated with a wide variety of human malignancies including Burkitt's lymphoma, gastric carcinomas, nasopharyngeal carcinoma, T-cell lymphomas, Hodgkin's disease, post-transplant lymphoma-like disease (PTLD), and leiomyosarcomas. EBV can directly transform human B cells in culture through expression of a subset of viral genes commonly known as latent genes. One or more latent genes are expressed in all EBV-associated malignancies. Identifying the functions of EBV latent genes that mediate B cell immortalization is a first step towards understanding the pathogenic role the virus has in the aforementioned malignancies.
The long-term goal of this research program is to understand how two EBV latent proteins, known as EBNA2 and EBNA-LP, contribute to EBV-driven B cell immortalization. EBNA2 is a transcriptional activator of cellular and viral latent genes and functions in part by mimicking cellular Notch signaling. EBNA-LP appears to function as a co-activator of EBNA2. We are currently using genetic, biochemical, molecular, and transgenic mouse approaches to understand the mechanisms by which these proteins function, identify the cellular cofactors required for these functions, and determine their role in virus-induced cellular proliferation. Understanding how EBV latent proteins function is likely to provide valuable insight into the mechanisms of EBV-mediated B cell immortalization, the pathogenesis of EBV-associated malignancies, viral persistence, and possibly B cell biology in general.

Ling Lab Website

International Association for Research on Epstein-Barr virus and Associated Diseases

Recent Publications (PubMed)

Gordadze, A.V., Onunwor, C.W., Peng, R.S., Kremmer, E., and P.D. Ling. 2004. EBNA2 amino acids 2-30 are required for induction of LMP-1 and immortalization maintenance. J. Virol. 78:3919-3929.

Walling, D.M., Ling, P.D., Gordadze, A.V., Walters-Montes, M., Flaitz, C.M., and C.M. Nichols. 2004. EBV Gene Expression in Hairy Leukoplakia. JID 190:396-399.

Lee, J.M., Lee K.H., Farrell, C.J., Ling P.D., Kempkes, B., Park, J.H., and S.D. Hayward. 2004. EBNA2 is required for protection of latently Epstein-Barr virus infected B cells against specific apoptotic stimuli. J. Virol. 78:12694-12697.

Peng, R.S., Moses, S.M., Tan J.T., Kremmer, E., and P.D. Ling. 2005. The Epstein-Barr virus EBNA-LP protein preferentially co-activates EBNA2-mediated stimulation of latent membrane proteins expressed from the viral divergent promoter. J. Virol. 79:4492-4505.

Ling, P. D., and H. H. Huls. 2005. Isolation and Immortalization of Lymphocytes. In F. M. Ausubel, R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, and K. Struhl (ed.), Current protocols in Molecular Biology. John Wiley & Sons, Inc. (In Press).

Ling, P.D., Peng, R.S., Nakajima, A., Yu, J.H., Tan, J., Moses, S.C., Yang, W-H., Zhao, B., Kieff, E., Bloch, K.D., and D.B. Bloch. 2005. Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by the PML nuclear body-associated protein Sp100. (EMBO J, in press).